1. Field of the Invention
The present invention relates to an improved process for the preparation of chloropyrimidines.
2. Discussion of the Background
Chloropyrimidines are of great commercial interest as intermediates for new, highly effective pesticides and pharmaceuticals. In many methods for the preparation of chloropyrimidines, amines, preferably N,N-dimethylaniline or N,N-diethylaniline, or amine hydrochlorides are added in accordance with the procedures outlined in D. J. Brown, The Pyrimidines, 162-167 (1962) in order to improve yields. In this conventional process, after removal of the excess POC1.sub.3 by distillation, the resulting reaction mixture is taken up in ice-water and the chloropyrimidine is extracted from the aqueous phase or removed by filtration.
However, this process can not be used for the preparation of relatively large quantities on an industrial scale due to the high risk of uncontrollable heat generation during the aqueous work-up. Also, flocculent and slimy byproducts from the reaction render the extraction and filtration of the products from the aqueous phase difficult, and some chloropyrimidines are readily decomposed in water. A particular disadvantage, however, is the fact that large quantities of effluent are obtained which contain a very high quantity of phosphoric acid, amine hydrochlorides and other toxic by-products from the reaction.
If attempts are made to work up the reaction mixture by distillation once the POC1.sub.3 has been removed, severe decomposition of the chloropyrimidines and decomposition or sublimation of the amine hydrochlorides are observed, especially in the case of large batches. Furthermore, there remain large quantities of highly viscous residues which contain polymeric phosphorus compounds and other decomposition products. Disposal of these polymeric and other decomposition products is difficult, making this work-up procedure also unusable for the industrial preparation of relatively large quantities of chloropyrimidines.
A substantial improvement to the process for preparing chloropyrimidines is described in DE-A-22 48 747, which discloses that the polymeric phosphorus compounds, which are obtained as by-products of many reactions involving POC1.sub.3 or POBr.sub.3, are converted back to POC1.sub.3 or POBr.sub.3, respectively, using phosphorus pentahalides, which may also be produced in situ. Removal of the phosphoryl halides, by distillation, leaves the reaction product together, if appropriate, with the catalyst used. If this process is applied to the preparation of chloropyrimidines, then the distillative removal of the excess POC1.sub.3 leaves a mixture of the chloropyrimidine and the amine hydrochloride. In DE A-22 48 747, such a mixture is taken up in water and acid at from 60.degree. to 80.degree. C., the product is separated off and the amine is liberated from the aqueous phase by adding sodium hydroxide solution and extracting with toluene. The extracts are then fractionally distilled to recover about 68% of the amine.
However, this process also has great disadvantages. Here too the presence of flocculent, slimy by-products, which are difficult to remove by filtration, makes the separation of the product from the aqueous phase extremely difficult, even when solvents are added for extraction. Also, in the case of relatively sensitive chloropyrimidines, there is the risk of decomposition by hydrolysis. The complicated recovery of the amine by addition of sodium hydroxide solution followed by extraction from the aqueous phase is likewise hindered by poor phase separation, and tends to leave behind an aqueous phase which still contains residues of toxic, chlorinated organic compounds and amines which are toxic and not readily degradable.
The work-up method disclosed in DE A-22 48 747, involves the distillative removal of the phosphoryl chloride, followed directly by distillation of the product. However this work-up is unsuccessful when amine or amine hydrochloride is present in the reaction mixture. In such cases, severe encrustation and decomposition are observed even when vacuum distillations are employed.